The principal aim of the clinical treatment of fractures is to immobilize the fracture fragment so that bony union proceed. However, the nature of the repair process is greatly affected by the local mechanical conditions. Direct cortical reconstruction, callus formation, and nonunion, are related to the level of interfragmentary motion which in turn is related to the rigidity of fixation. The relative merits of primary and secondary bone healing are widely debated. Also, little is known about how the local strain environment influences the vascular and cellular processes that constitute fracture healing. Perren and co-workers provided a comprehensive "interfragmentary strain" hypothesis describing the influence of the local mechanical environment on the morphology of fracture healing. They suggest that a repair tissue can only be formed if the tissue tolerates the local mechanical strain. Using finite element modeling techniques, we have shown that the interfragmentary strains are complex, with severe strain gradients both across the cortex and along the endosteal and periosteal surfaces. Based on these insights, our objectives with this research program are to provide a critical test of Perren's hypothesis. In experiments to be funded separately and conducted at the Laboratory for Experimental Surgery in Davos, Switzerland, Perren and co-workers will provide an in vivo model for the investigation of this hypothesis. The mid-diaphysis of sheep tibiae will be osteotomized and fixed with a modified internal fixation plate to produce a uniform 2 mm gap. Hydraulic actuators applied to transcutaneous pins will produce cyclic bending deformations of the healing osteotomy. The applied deformations in the first series will be such that abundant callus formation will be expected at the plate-far cortex, similar to pilot experiments. The applied deformations in the second series will be such that regions of primary and secondary bone healing will be expected. Computed tomography, polychrome labels, and an intravital die will be used to document the healing process. The histologic sections will be analyzed with the collaboration of Perren and co-workers to characterize the healing process and quantify the vascularity and bone porosity. The mechanical properties of the interfragmentary tissues will be measured and representative finite element models will be generated. An iterative solution scheme will be used to predict fragment end resorption based on a tensor failure criterion applied to the gap material. The interfragmentary strain hypothesis will be tested by comparing the finite element predictions of failure strains and bone resorption to the histologic data.